New drug targets Hard-to-Treat cancers with KRAS G12D mutation

NCT ID NCT05382559

Disease control Sponsor: Astellas Pharma Inc Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jul 31, 2026 · Updated 7 times

Summary

This study tests a new drug called ASP3082 in people with advanced solid tumors that have a specific genetic change called KRAS G12D. The trial has two parts: first, finding a safe dose of ASP3082 alone or with another drug; second, testing it with other cancer treatments. Up to 681 participants will receive the drug through an IV. The main goals are to check safety and find the best dose.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Setidegrasib (ASP3082) and various chemotherapy drugs
What this could lead to: If successful, this could lead to a new treatment option for people with advanced solid tumors that have the KRAS G12D mutation.
What could go wrong: This is an early Phase 1 trial focused on safety, not yet on effectiveness. The drug may not work or could cause side effects. Results may not apply to all patients.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1

The first testing in people. Mainly checks safety and dose, usually in a small group.

Participants

About 681 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jun 2022

Expected to finish

Dec 2028

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Participant has locally advanced (unresectable) or metastatic solid tumor malignancy with documented Kirsten rat sarcoma viral oncogene homolog \[KRAS\] G12D mutation and has received prior standard therapy and the investigator does not see any further clinical benefit from continuing such targeted therapy, or is ineligible to receive standard approved therapies (no limit to the number of prior treatment regimens). * For the ASP3082 monotherapy escalation cohorts, participants with solid tumor malignancies are allowed to be enrolled. Participants with other known KRAS G12 mutations will not be eligible for the study * For ASP3082 combination therapy with Nab-P+GEM or FOLFIRINOX or NALRIFOX: Participant must have mPDAC that has not been previously treated with chemotherapy. If a participant received (neo)adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the (neo)adjuvant therapy. * Participant consents to provide tumor specimen in a tissue block or unstained serial slides or a tumor biopsy (core needle biopsy or excision) obtained after the last interventional treatment, but prior to start of study intervention. Participant also consents to provide a sample for tumor biopsy during the treatment period as indicated in the study protocol. If a participant cannot provide a fresh tissue biopsy sample, the site should consult with the sponsor/study medical monitor. * Participant has at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Participant has an ECOG performance status of 0, 1 or 2 for dose escalation, and 0 or 1 for dose expansion. * Participant's last dose of prior antineoplastic therapy, including any immunotherapy, was 21 days or 5 half-lives, whichever is shorter, prior to initiation of study intervention administration. * Participant has completed any radiotherapy (including stereotactic radiosurgery) at least 14 days prior to the start of study intervention administration. Participants must have recovered from all radiation-related toxicities, not require corticosteroids (NOTE: Physiologic replacement dose of hydrocortisone or its equivalent \[defined as up to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone, or up to 10 mg per day of prednisone\] is permitted), and not have active radiation pneumonitis. A 1-week washout is permitted for palliative radiation (\<= 2 weeks of radiotherapy) to non-central nervous system disease. * Participant's adverse events \[AEs\] (excluding alopecia) from prior therapy have improved to grade 1 or baseline within 14 days prior to start of study intervention (or prior to staring SoC chemotherapy, for first line (1L) participants receiving Nab-P+GEM FOLFIRINOX or NALIRIFOX. * Participant has adequate organ function as indicated by protocol laboratory value parameters (If a participant has received a recent blood transfusion, the laboratory tests must be obtained \>= 14 days after any blood transfusion.). * Female participant is not pregnant, confirmed by pregnancy test and medical evaluation by interview, and at least 1 of the following conditions apply: * Not a woman of childbearing potential (WOCBP). * WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after study intervention administration. * EU only: For combination therapy with carboplatin, follow contraception guidelines from the time of informed consent through at least 7 months after the final dose of carboplatin. * South Korea only: For combination therapy with oxaliplatin, follow contraception guidelines from the time of informed consent through at least 15 months after the final dose of oxaliplatin. For combination therapy with cisplatin, follow contraception guidelines from the time of informed consent through at least 14 months after the final dose of cisplatin. * Female participant must agree not to breastfeed starting at screening and throughout the study period and for 6 months after study intervention administration. * Female participant must not donate ova starting at first dose of study intervention and throughout the study period and for 6 months after study intervention administration. * Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 3 months after study intervention administration. * Male participant must not donate sperm during the treatment period and for 3 months after study intervention administration. * South Korea only: For combination therapy with oxaliplatin, follow contraception guidelines from the time of informed consent through at least 12 months after the final dose of oxaliplatin. For combination therapy with cisplatin, follow contraception guidelines from the time of informed consent through at least 11 months after the final dose of cisplatin. * Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 3 months after study intervention administration. * Participant agrees not to participate in another interventional study while receiving study intervention (Participants who are currently in the follow-up period of an interventional clinical trial are allowed). * For ASP3082 Combination Therapy with Pembrolizumab (Cohort G), or Platinum-based Chemotherapy + Pemetrexed +/- Pembrolizumab (Cohort H): Participant must have pathologically documented locally advanced or metastatic (unresectable Stage IIIB-IV) non-small cell lung cancer (NSCLC) (Note: for Cohort H only, the tumor must be non-squamous NSCLC) with KRAS G12D mutation and * have received prior platinum-containing chemotherapy (safety lead-in only) or * have never received systemic therapy (up to 1 cycle of SoC pembrolizumab \[defined as one 21-day cycle of 200 mg\] in Cohort G and up to 1 cycle of SoC platinum-based chemotherapy ± pembrolizumab \[defined as one 21-day cycle of 200 mg\] or pembrolizumab \[defined as one 21-day cycle of 200 mg\] in Cohort H is permitted prior to Screening, provided a 21-day washout occurs before C1D1) for locally advanced or metastatic NSCLC with no oncogenic driver mutations. Participants who received adjuvant or neoadjuvant platinum-based chemotherapy and developed recurrent or metastatic disease more than 12 months after completing therapy may be enrolled. Exclusion Criteria: * Participant has received investigational therapy within 21 days or 5 half-lives, whichever is shorter, prior to start of study intervention. * Participant has symptomatic or untreated central nervous system (CNS) metastases. Participants with asymptomatic, treated CNS metastases are eligible. * Participant has leptomeningeal disease as a manifestation of the current malignancy. * Participant has a prior malignancy active (i.e., requiring treatment or intervention) within the previous 2 years, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed. * Participant has a known or suspected hypersensitivity to ASP3082 or any components of the formulation used. * Participant with active hepatitis B (including acute hepatitis B virus \[HBV\] or chronic HBV) or hepatitis C virus \[HCV\] (ribonucleic acid \[RNA\] detected by qualitative assay). HCV RNA testing is not required in participants with negative HCV antibody testing. * Participant has a known history of human immunodeficiency virus \[HIV\] infection. No HIV testing is required unless mandated by a local health authority. * Participant has had a myocardial infarction or unstable angina within 6 months prior to the start of study intervention, left ventricular ejection fraction (LVEF) \< 50% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO) or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, obligate use of a cardiac pacemaker, or long QT syndrome. * Participant has a corrected QT interval (single electrocardiogram \[ECG\]) using Fridericia's formula (QTcF) \> 450 milliseconds (msec) (men) or \>470 msec (women) during screening. * Participant has received prior treatment with a specific KRAS G12D inhibitor/degrader or pan-RAS inhibitor/degrader targeting KRAS G12D. Participants who received prior treatment with a KRAS G12D inhibitor/degrader are eligible for the ASP3082 combination therapy cohort. * Participant has an active infection requiring intravenous antibiotics within 14 days prior to study intervention. * Participant is expected to require another form of antineoplastic therapy while on study treatment. * Participant has any condition which makes the participant unsuitable for study participation (such as psychiatric illness/social situations that would limit compliance with study requirements). * Participant has had major surgery within 4 weeks prior to first dose of study intervention. For ASP3082 Combination Therapy: * Prior discontinuation of cetuximab treatment due to toxicity or intolerance of cetuximab. * History of interstitial lung disease requiring systemic steroid treatment. Note that a participant with resolved pulmonary infections or radiation pneumonitis is eligible.

Get updates

Get notified about this study

Vår säkerhetsrekommendation!

Genom att skicka in godkänner du våra Användarvillkor

Conditions

The condition(s) this trial relates to.

neoplasm Neoplasm Metastasis

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Solid tumor

How to take part

Only the study team decides who joins. These are the ways to reach them.

The places running it

65 sites in 7 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

Aichi Cancer Center
RECRUITING

Nagoya, Aichi-ken, Japan
Beijing Cancer Hospital
RECRUITING

Beijing, Beijing Municipality, China
Beth Israel Deaconess Medical Center
RECRUITING

Boston, Massachusetts, 02215, United States
Cancer Institute Hospital of JFCR
RECRUITING

Koto-ku, Tokyo, Japan
Case Western
RECRUITING

Cleveland, Ohio, 44106, United States
City of Hope National Medical Center
RECRUITING

Duarte, California, 91010, United States
Columbia University - Herbert Irving Comprehensive Cancer Center
RECRUITING

New York, New York, 10032, United States
Dana Farber Cancer Institute
RECRUITING

Boston, Massachusetts, 02215, United States
Denver HealthONE Drug Development Unit
RECRUITING

Denver, Colorado, 80218, United States
Florida Cancer Specialist
RECRUITING

Lake Mary, Florida, 32746, United States
Florida Cancer Specialists & Research Institute Sarasota
RECRUITING

Sarasota, Florida, 34232-6422, United States
Fudan University Shanghai Cancer Center
RECRUITING

Xuhui District, Shanghai Municipality, China
Georgetown University Hospital
RECRUITING

Washington D.C., District of Columbia, 20007, United States
Hackensack University Medical Center
RECRUITING

Hackensack, New Jersey, 07601, United States
Hokkaido University Hospital
RECRUITING

Sapporo, Hokkaido, Japan
Kanagawa Cancer Center
RECRUITING

Yokohama, Kanagawa, Japan
Kansai Medical University Hospital
RECRUITING

Hirakata, Osaka, Japan
Kindai University Hospital
RECRUITING

Sayama, Osaka, Japan
Kurume University Hospital
RECRUITING

Kurume, Fukuoka, Japan
Memorial Sloan Kettering Cancer Center
RECRUITING

New York, New York, 10065, United States
NEXT Oncology
RECRUITING

San Antonio, Texas, 78229, United States
NEXT Oncology - Virginia Cancer Specialists
RECRUITING

Fairfax, Virginia, 22031, United States
National Cancer Center Hospital
RECRUITING

Chuo-ku, Tokyo, Japan
National Cancer Center Hospital East
RECRUITING

Kashiwa, Chiba, Japan
Niigata Cancer Center Hospital
RECRUITING

Niigata, Niigata, Japan
Oregon Health and Science University
RECRUITING

Portland, Oregon, 97239, United States
Osaka International Cancer Institute
RECRUITING

Osaka, Japan
PanOncology Trials
RECRUITING

San Juan, 00935, Puerto Rico
Roswell Park Cancer Institute
RECRUITING

Buffalo, New York, 14263, United States
SCRI Oncology Partners
TERMINATED

Nashville, Tennessee, 37203, United States
Shanghai Pulmonary Hospital
RECRUITING

Shanghai, China
Shikoku Cancer Center
RECRUITING

Matsuyama, Ehime, Japan
Shizuoka Cancer Center
RECRUITING

Sunto-gun, Shizuoka, Japan
Site ES34001
RECRUITING

Barcelona, Spain
Site ES34002
RECRUITING

Málaga, Spain
Site ES34003
RECRUITING

Seville, Spain
Site ES34004
RECRUITING

Madrid, Spain
Site ES34005
RECRUITING

Barcelona, Spain
Site ES34006
RECRUITING

Madrid, Spain
Site ES34009
RECRUITING

A Coruña, Spain
Site ES34010
RECRUITING

Valencia, Spain
Site ES34011
RECRUITING

Pamplona, Navarre, Spain
Site FR33001
RECRUITING

Lyon, France
Site FR33002
RECRUITING

Bordeaux, France
Site FR33003
RECRUITING

La Tronche, Grenobele, France
Site FR33004
RECRUITING

Villejuif, Île-de-France Region, France
Site FR33005
RECRUITING

Lyon, France
Site KR82001
RECRUITING

Jongno -Gu, Seoul, South Korea
Site KR82002
RECRUITING

Seongnam-si, Gyeonggi-do, South Korea
Site KR82003
RECRUITING

Seodaemun-gu, Seoul, South Korea
Site KR82004
RECRUITING

Songpa-gu, Seoul, South Korea
Site KR82005
RECRUITING

Goyang-si, Gyeonggi-do, South Korea
Site KR82006
RECRUITING

Seoul, South Korea
Site KR82007
RECRUITING

Cheongju-si, North Chungcheong, South Korea
Smilow Cancer Center at Yale New Haven Hospital
RECRUITING

New Haven, Connecticut, 06520-8028, United States
Taylor Cancer Research Center
RECRUITING

Maumee, Ohio, 43537, United States
Tohoku University Hospital
RECRUITING

Sendai, Miyagi, Japan
Trinity Health Ann Arbor Hospital
RECRUITING

Ypsilanti, Michigan, 48197, United States
UCLA Santa Monica Hematology Oncology
RECRUITING

Santa Monica, California, 90404, United States
University of Florida, Davis Cancer Center
RECRUITING

Gainesville, Florida, 32610, United States
University of Kansas Medical Center
RECRUITING

Westwood, Kansas, 66205, United States
University of Rochester Medical Center James P. Wilmot Cancer Center
RECRUITING

Rochester, New York, 14642, United States
University of Wisconsin Hospital
RECRUITING

Madison, Wisconsin, 53792, United States
Vanderbilt University Medical Center
RECRUITING

Nashville, Tennessee, 37232, United States
Washington University School of Medicine
RECRUITING

St Louis, Missouri, 63110, United States
Yamaguchi University Hospital
RECRUITING

Ube, Yamaguchi, Japan

More trials for these conditions

Other studies related to the condition(s) this trial covers.